Cocaine abuse alone, and co-ocurring with heroin dependence, have substantial individual and societal consequences. The Substance Abuse Research Center group, Department of Psychiatry, University of Texas Health Science Center-Houston and the Center for Addiction Research, University of Texas Medical Branch-Galveston, are devoted to development and screening of effective pharmacotherapies. Activities include Scientific/Administrative oversight, and implementation of specific preclinical, human laboratory, CRC inpatient, and Treatment Research Clinic outpatient studies. The themes include medication screening and development, specification of intervention points in disease course (ongoing v abstinence), and delineation of optimal medications alone and in combination. The research and clinical activity include a substantial interdisciplinary training component. The aims will be accomplished through four component projects listed below: 1. Scientific Project-Cocaine/Heroin: Pharmacotherapy Dosing Regimens. 2. Scientific Project-Screening Medications for Cocaine Cessation and Relapse Prevention. 3. Scientific Project-lmpulsivity, Brain Function & Substance Abuse Treatment. 4. Scientific Project-Drug Effects on Oral cocaine-Reinforced Behavior.